Formyl peptide receptor 2 regulates monocyte recruitment to promote intestinal mucosal wound repair

• Type of Material: Article
• Authors: Dorothee Birkl, University of Michigan; Monique N. O'Leary, University of Michigan; Miguel Quiros, University of Michigan; Veronica Azcutia, University of Michigan; Matthew Schaller, University of Michigan; Michelle Reed, University of Michigan; Hikaru Nishio, Emory University; Justin Keeney, University of Michigan; Andrew Neish, Emory University; Nicholas W. Lukacs, University of Michigan; Charles A. Parkos, University of Michigan; Asma Nusrat, Emory University
• Language: English
• Date: 2019-12-01
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © FASEB
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1096/fj.201901163R
• Title of Journal or Parent Work: FASEB JOURNAL
• Volume: 33
• Issue: 12
• Start Page: 13632
• End Page: 13643
• Grant/Funding Information: This work was supported by U.S. National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases Grants DK055679, DK089763, and DK059888 (to A.N.) and DK072564, DK079392, and DK061379 (to C.A.P.); German Research Foundation (DFG) Research Fellowship SI 2282/1-1 (to D.B.); and Crohn’s and Colitis Foundation Career Development Award 544599 (to M.Q.). The authors declare no conflicts of interest.
• Keywords: EPITHELIAL-CELLS; inflammation; RESPONSES; RESOLUTION; DENDRITIC CELLS; MACROPHAGES; INFLAMMATORY PROTEIN 3-ALPHA; MOUSE; GPCRs; INTERNATIONAL UNION; epithelium; Life Sciences & Biomedicine; ACTIVATION; FPR2; Cell Biology; Biology; Life Sciences & Biomedicine - Other Topics; inflammatory bowel disease; CROSS-DESENSITIZATION; Biochemistry & Molecular Biology; Science & Technology
• Research Categories: Biology, Cell

Abstract

Mucosal wound repair is coordinated by dynamic crosstalk between endogenous and exogenous mediators and specific receptors on epithelial cells and infiltrating immune cells. One class of such receptor-ligand pairs involves formyl peptide receptors (FPRs) that have been shown to influence inflammatory response and repair. Here we explored the role of murine Fpr2/3, an ortholog of human FPR2/receptor for lipoxin A4 (ALX), in orchestrating intestinal mucosal repair. Compared with wild-type (WT) mice, Fpr2/3-/- mice exhibited delayed recovery from acute experimental colitis and perturbed repair after biopsy-induced colonic mucosal injury. Decreased numbers of infiltrating monocytes were observed in healing wounds from Fpr2/3-/- mice compared with WT animals. Bone marrow transplant experiments revealed that Fpr2/3-/- monocytes showed a competitive disadvantage when infiltrating colonic wounds. Moreover, Fpr2/3-/- monocytes were defective in chemotactic responses to the chemokine CC chemokine ligand (CCL)20, which is up-regulated during early phases of inflammation. Analysis of Fpr2/3-/- monocytes revealed altered expression of the CCL20 receptor CC chemokine receptor (CCR)6, suggesting that Fpr2/3 regulates CCL20-CCR6-mediated monocyte chemotaxis to sites of mucosal injury in the gut. These findings demonstrate an important contribution of Fpr2/3 in facilitating monocyte recruitment to sites of mucosal injury to influence wound repair.-Birkl, D., O'Leary, M. N., Quiros, M., Azcutia, V., Schaller, M., Reed, M., Nishio, H., Keeney, J., Neish, A. S., Lukacs, N. W., Parkos, C. A., Nusrat, A. Formyl peptide receptor 2 regulates monocyte recruitment to promote intestinal mucosal wound repair.